Anthrax is a rare, but deadly disease and poses a serious threat as a bioterror agent. The current anthrax vaccine uses needle injection and requires repeated immunizations for inducing protection and frequent boosts for maintaining immunity, thus making it impractical for mass immunization against this rare disease. To protect against bioterror threats, an ideal anthrax vaccine would have the following desired features: 1) inducing immediate protection so that it can be used as an emergent prophylaxis, and 2) inducing long-lasting immunity by a single, simple immunization procedure suitable for mass immunization. We have tested a novel vaccine platform and our preliminary results indicate that this immunization strategy induce 1) a rapid innate response in the lung that may confer immediate protection against inhalational anthrax, and 2) stable memory B and T cells that will likely provide long-lasting immunity. The objective of this application is to develop new attenuated strains suitable and safe for further development and clinical testing of our novel vaccine platform. The specific aims of this Phase I STTR application are: 1) to construct new attenuated strains and test their virulence and potential as highly attenuated vaccine strains; 2) to test the ability of our new vaccine strains to induce the rapid innate response in the lung and to generate high levels of antibodies and long-lasting T cell memory. At the end of this Phase I study, we hope to identify new attenuated vaccine strains that are severely attenuated yet highly immunogenic. This will set the stage for the Phase II study in which we will test these new attenuated strains for inducing protective immunity against fully virulent B. anthracis in small animal models and non-human primates. With the combination of new attenuated strains and a novel vaccine platform, our ultimate goal is to develop a vaccination strategy suitable for mass immunization to induce immediate and long-term protective immunity against pulmonary anthrax. [unreadable] [unreadable]